It is the purpose of this proposal to continue to study the physiology of the gonadotropin releasing hormone, LHRH, in the male utilizing both in vivo and in vitro approaches. LHRH deficient males with idiopathic hypogonadotropic hypogonadism are able to synthesize and release gonadotropins which can elicit physiologic gonadal responses when administered exogenous LHRH. Long-term, out-patient LHRH administration via portable infusion pumps has been possible in these males with IHH permitting systematic variations in the dose and frequency of LHRH administration throughout sexual development. The effects of variations in the frequency of LHRH upon the ratio of gonadotropins secreted and the effects of these, in turn, upon gonadal secretion, can be undertaken with this mode. In addition, the Modulatory role of gonadal steroids and systematic alterations in LHRH frequency upon the biologic to immunologic ratios of gonadotropins can be approached in a human mode. As an adjunct to these studies dispersed, perifused rat pituiticyte systems have also been developed which will permit examination of LHRH stimulated gonadotropin release in vitro in the absence of endogenous gonadal steroid secretions. This experimental model system can be utilized in a parallel series of experiments designed to repeat the observations discovered in vivo and determine their precise mechanisms at the cellular level including study of LHRH receptors in messenger RNA for LH. Employing a combination of these two approaches, each with its unique experimental advantages, should provide insight into the role of LHRH's control of gonadotropin secretion, its modification, and physiologic regulation.
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